This project has two main goals: (1) to identify and isolate novel antibacterial compounds from natural sources (soil microorganisms), and (2) to train students in integrative approaches to research, combining microbiology and organic chemistry. Antibiotic chemotherapy has been increasingly compromised by the evolution of antibiotic resistant strains, and new antibiotic compounds are needed to replace or supplement those in current use. The original sources of many common antibiotics were soil microorganisms. This project continues that hunt, seeking bacteria that secrete novel compounds from soil samples collected from a wide range of sites. Varied laboratory growth conditions will be employed to extend the range of types of organisms cultured from these samples, including anaerobiosis and nutrient limited media. Bacterial species producing inhibitory chemicals will be identified in mixed competition cultures, then isolated and grown in pure cultures. The identity of these candidate antibiotic-producers will be determined by standard microbiological typing procedures, supplemented with molecular techniques (PFGE). Conditioned media from these pure cultures will be treated to extract and purify the active antibacterial compounds by standard and HPLC-based chromatography. The composition and structure of these compounds will be determined using spectroscopic techniques, and the results compared with known antibacterial agents. Novel compounds will be candidates for later work (not described here) determining the usefulness of these agents for disease chemotherapy. Student researchers participating in this project will experience the integration of fields normally taught as separate disciplines. Their continued success as scientists, and their contributions to advancements in human health will be enhanced by a multidisciplinary approach to research.